The main goal of the Giraldez Laboratory is to understand the cellular and molecular signals that initiate embryonic development and to uncover universal principles that direct the development of a new life. In addition to this, we are applying our knowledge of mRNA regulation to engineer therapeutic mRNAs for gene therapy and vaccine development.
A universal step in all animals is the maternal-to-zygotic transition, whereby the transcriptionally silent egg activates the new zygotic program and removes the old maternal program. This central step in animal development can be considered the beginning of life from a transcriptional standpoint, as subsequent developmental decisions will depend on the correct activation of the zygotic program and regulation of the previous maternal program..
The questions: How does the vertebrate embryo activate the silent zygotic genome? How does the embryo regulate mRNAs post-transcriptionally to regulate the previous developmental program? And how can we use this understanding to design therapeutic mRNAs that are stable, tissue-specific, and capable of treating diseases? The approaches:?
The approaches: We have a multidisciplinary infrastructure (wet/dry) that allows us to combine genomics, embryology, biochemistry, and computational biology. This enables us to leverage the powerful genetics in zebrafish/mouse/cell culture to understand vertebrate development while also applying these insights to create therapeutic mRNAs for gene therapy and vaccines.
The Giraldez Lab is part of the Yale Combined Program in the Biological and Biomedical Sciences (BBS). Interested students should send Antonio an e-mail to arrange a meeting.
Rotation projects in 2024-2025 are focused on understanding the regulatory signals that shape mRNA stability across the 5’ UTR, CDS and 3’ UTRs, understanding how the cell recognizes and overcome stop codons, and how different sequences and structural elements regulate mRNA stability and translation across different cell types with the goal of understanding the post-transcriptional mechanisms of gene regulation and engineer better therapeutic mRNAs.